Efficacy of two alternate vaccines based on Plasmodium falciparum merozoite surface protein 1 in an Aotus challenge trial

In an attempt to produce a more defined, clinical-grade version of a vaccin e based on Plasmodium falciparum merozoite surface protein 1 (MSP1), we eva luated the efficacy of two recombinant forms of MSP1 in an Aotus nancymai c hallenge model system. One recombinant vaccine, bvMSP1(42), based on the 42 -kDa C-terminal portion of MSP1, was expressed as a secreted protein in bac ulovirus-infected insect cells. A highly pure baculovirus product could be reproducibly expressed and purified at yields in excess of 8 mg of pure pro tein per liter of culture. This protein, when tested for efficacy in the Ao tus challenge model, gave significant protection,,vith only one of seven mo nkeys requiring treatment for uncontrolled parasitemia after challenge with P. falciparum, The second recombinant protein, P30P2MSP1(19), has been use d in previous studies and is based on the smaller, C-terminal 19-kDa portio n of MSP1 expressed in Saccharomyces cerevisiae. Substantial changes were m ade in its production process to optimize expression. The optimum form of t his vaccine antigen las judged by in vitro and in vivo indicators) was then evaluated, along with bvMSP1(42), for efficacy in the A. nancymai system. The new formulation of P30P3MSP1(19) performed significantly worse than bvM SP1(42) and appeared to be less efficacious than we have found in the past, with four of seven monkeys in the vaccinated group requiring treatment for uncontrolled parasitemia. With both antigens, protection was seen only whe n high antibody levels were obtained by formulation of the vaccines in Freu nd's adjuvant, Vaccine formulation in an alternate adjuvant, MF59, resulted in significantly lower antibody titers and no protection.